When treating patients with CLL, understanding specific details about the disease helps doctors as they choose among available treatments. CLL experts believe that conducting specific blood tests before prescribing each patient’s treatment is critical. Do all doctors who treat patients with CLL also appreciate this need for testing?

Some treatments for chronic lymphocytic leukemia (CLL) are more effective when the patient’s cancer cells have certain features, such as specific genetic mutations or other markers (eg, biomarkers) of the disease. Other treatments do not work well based on the presence of certain genetic mutations. The only way to learn whether a patient with CLL has these mutations is to test their blood. However, recent data suggest that not all cancer specialists, known as oncologists, test all their patients with CLL.

Two different sets of data have been analyzed to learn how often oncologists test their patients with CLL. The older of these, called Connect CLL, looked at testing practices in 199 medical centers in the United States between 2010 and 2014. During this time, testing was less important because newer targeted drugs were not yet available. Since 2014, new drug approvals have shifted experts’ understanding of the value of genetic testing in CLL. There is now clear evidence that many newer treatments are dramatically better for certain patients with CLL who have specific mutations.

The second data set is from a registry called informCLL, which gathered information about patient care from 150 US cancer centers (96% community and 4% academic centers) between 2015 and 2018. During this time, the value of testing in CLL treatment choices had become clearer. One would expect that appropriate testing of patients with CLL would be more common in this database. Surprisingly, these data show that rates of laboratory testing for patients with CLL have fallen.

Three key tests that should be performed before doctors choose treatments for patients with CLL are:

FISH. FISH, which stands for fluorescence in situ hybridization, evaluates CLL cells for chromosome abnormalities. One of the most important is the finding of a deletion of the short arm of the 17th chromosome. The presence of deletion 17p or del(17p) strongly predicts poor response to chemotherapy drugs, such as chlorambucil, fludarabine, and cyclophosphamide.

TP53 Mutation Testing.TP53 is a gene on the short arm of the 17th chromosome that helps chemotherapy to suppress cancer growth. When TP53 ismissing or mutated, chemotherapy generally does not work as well.

IGHV Mutation Testing. Patients with CLL and an unmutated IGHV gene generally have a shorter progression time if they receive chemotherapy.

Cancer guidelines recommend that all these tests should be done before choosing a patient’s first treatment. FISH testing and TP53 mutation testing should be done again before selecting subsequent treatments for CLL; these test results can change over time, typically for the worse. A patient’s IGHV mutation status is almost always stable over time; it does not need to be retested.

Connect CLL Registry: 2010-2014

Less than two-thirds of patients with CLL underwent FISH testing at the time they needed treatment.

Only 6% of patients with CLL had IGHV mutation testing performed before receiving their first treatment for CLL.

Only 40% of patients who relapsed after their initial treatment for CLL had repeat FISH testing before moving on to their therapy.

informCLL Registry: 2015-2018

Less than one-third (31%) of patients with CLL had FISH testing, 11% had TP53 mutation testing, and 11% had IGHV mutation testing at the time they needed treatment.

Among patients with relapsed or refractory CLL, rates were even lower: 26% had testing for FISH, 9% for TP53, and 10% for IGHV.

These databases also show that a significant minority of patients with CLL received chemotherapy, despite test results showing that this treatment would not work as well as targeted treatments. CLL is relatively uncommon, and some oncologists treat fewer patients with CLL than others. As a result, some oncologists may not be aware of the latest testing recommendations for patients with CLL. Registries such as these are critical in helping oncologists and patients to understand practice patterns and identify opportunities for education.

The chemotherapy-free combination of venetoclax plus obinutuzumab has shown efficacy and tolerability in older patients with chronic lymphocytic leukemia. Adding acalabrutinib, a new targeted agent, may enhance the clinical benefits of this regimen, according to results of a clinical trial.

Alliance A041702 is a large clinical trial that is exploring whether adding venetoclax to the combination of ibrutinib and obinutuzumab can improve outcomes in patients with chronic lymphocytic leukemia.

According to results from a recent study, patients with chronic lymphocytic leukemia are more likely to survive for longer time periods if their posttreatment tests show no evidence of residual disease.

Last modified: February 12, 2020

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